CN108187134B - Preparation method of medical polylactic acid in-situ modified calcium phosphate cement 3D printing material - Google Patents
Preparation method of medical polylactic acid in-situ modified calcium phosphate cement 3D printing material Download PDFInfo
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- CN108187134B CN108187134B CN201810054143.9A CN201810054143A CN108187134B CN 108187134 B CN108187134 B CN 108187134B CN 201810054143 A CN201810054143 A CN 201810054143A CN 108187134 B CN108187134 B CN 108187134B
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 title claims abstract description 108
- 239000000463 material Substances 0.000 title claims abstract description 64
- 238000010146 3D printing Methods 0.000 title claims abstract description 57
- 239000004626 polylactic acid Substances 0.000 title claims abstract description 53
- 229920000747 poly(lactic acid) Polymers 0.000 title claims abstract description 52
- 238000011065 in-situ storage Methods 0.000 title claims abstract description 42
- 239000004568 cement Substances 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 239000000843 powder Substances 0.000 claims abstract description 47
- 239000001506 calcium phosphate Substances 0.000 claims description 39
- 238000001914 filtration Methods 0.000 claims description 36
- 238000006243 chemical reaction Methods 0.000 claims description 35
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 33
- 235000011010 calcium phosphates Nutrition 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
- 238000001035 drying Methods 0.000 claims description 27
- 238000005406 washing Methods 0.000 claims description 27
- 238000010438 heat treatment Methods 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 238000002156 mixing Methods 0.000 claims description 20
- 239000003960 organic solvent Substances 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 18
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 16
- 229910000271 hectorite Inorganic materials 0.000 claims description 15
- KWLMIXQRALPRBC-UHFFFAOYSA-L hectorite Chemical compound [Li+].[OH-].[OH-].[Na+].[Mg+2].O1[Si]2([O-])O[Si]1([O-])O[Si]([O-])(O1)O[Si]1([O-])O2 KWLMIXQRALPRBC-UHFFFAOYSA-L 0.000 claims description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims description 10
- OEOIWYCWCDBOPA-UHFFFAOYSA-N 6-methyl-heptanoic acid Chemical compound CC(C)CCCCC(O)=O OEOIWYCWCDBOPA-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 238000000227 grinding Methods 0.000 claims description 10
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 10
- 125000001979 organolithium group Chemical group 0.000 claims description 10
- 229910000275 saponite Inorganic materials 0.000 claims description 10
- 238000007599 discharging Methods 0.000 claims description 9
- 239000012065 filter cake Substances 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 6
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 6
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 6
- VBIIFPGSPJYLRR-UHFFFAOYSA-M Stearyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)C VBIIFPGSPJYLRR-UHFFFAOYSA-M 0.000 claims description 5
- 238000004321 preservation Methods 0.000 claims description 5
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 4
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- SZEMGTQCPRNXEG-UHFFFAOYSA-M trimethyl(octadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)C SZEMGTQCPRNXEG-UHFFFAOYSA-M 0.000 claims description 3
- -1 hectorite modified calcium phosphate Chemical class 0.000 claims description 2
- 230000008901 benefit Effects 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 7
- 210000000988 bone and bone Anatomy 0.000 description 17
- 230000007547 defect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Abstract
The invention relates to the technical field of 3D printing materials, in particular to a preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material. The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material comprises the following steps: step one, preparing organohectorite; step two, preparing organohectorite modified calcium phosphate powder; and step three, preparing the 3D printing material. The method has low cost and simple process. The medical polylactic acid in-situ modified calcium phosphate cement 3D printing material prepared by the preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material has the advantages of excellent mechanical strength, mechanical property and flexibility. Moreover, the preparation method has strong practicability and extremely bright industrial prospect.
Description
Technical Field
The invention relates to the technical field of 3D printing materials, in particular to a preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material.
Background
Patients with bone defects are increasing year by year due to aging, trauma, bone disease, and many other causes worldwide. Accordingly, there is an increasing demand for bone defect repair materials. The conventional bone repair method is mainly the transplantation of autologous bone and allogeneic bone, but because of the problems of immune rejection, limited supply source, secondary operation and the like which are difficult to overcome, the conventional bone transplantation method is gradually reduced, and meanwhile, the use of artificial bone repair materials is rapidly increased. In the field of artificial medical bone tissue materials, Calcium Phosphate Cement (CPC) using Calcium phosphate materials (mainly amorphous Calcium phosphate, tricalcium phosphate, tetracalcium phosphate, and the like) as main active components is widely applied to a plurality of clinical occasions due to excellent performances such as good biocompatibility, good osteoconductivity, degradation activity coordinated with osteogenesis activity, self-curing, and the like.
The main advantages of medical CPC: (1) the CPC microspheres can be randomly filled at irregular bone defects, and can form a three-dimensional pore structure which is mutually communicated in the process of stacking and filling, thereby being beneficial to the ingrowth of bone tissues and angiogenesis. (2) CPC has the advantages of good biocompatibility, good osteoconductivity and the like, so that the probability of needing adjuvant drugs for treatment after operation is greatly reduced. Because of this, CPC is used as a 3D printing material, and a bone tissue material is prepared by a 3D printing technology, and has been widely used in industries in the fields of clinical bone replacement and repair, etc. in developed countries.
However, CPC also has many clinical application problems, and the most fundamental key technical problem is that the mechanical strength and mechanical properties of bone tissue after CPC is cured are not particularly satisfactory. The fundamental reason is that the brittleness and the poor flexibility of the bone tissue after the CPC is cured are mainly caused, and the generated internal stress is difficult to quickly dissipate after the bone tissue is subjected to a great external force, so that the bone tissue after the CPC is cured cannot withstand the great external force to cause structural damage.
Disclosure of Invention
The invention aims to provide a preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material aiming at the defects of the prior art, and the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material prepared by the preparation method has the advantages of excellent mechanical strength, mechanical property and flexibility.
In order to achieve the purpose, the invention adopts the following technical scheme:
the preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material comprises the following steps:
step one, preparing organolithium saponite: firstly, dispersing hectorite in water at a certain temperature, and simultaneously dispersing quaternary ammonium salt in the water at the certain temperature to respectively obtain hot solutions; then mixing the two hot solutions, heating to a certain temperature, stirring and reacting for a certain time; then washing, filtering and drying at a certain temperature to constant weight to obtain the organohectorite;
step two, preparing the organohectorite modified calcium phosphate powder: adding the organohectorite and calcium phosphate powder prepared in the step one into absolute ethyl alcohol, heating to a certain temperature, keeping the temperature for a certain time, then washing, filtering, and drying at a certain temperature to constant weight to obtain organohectorite modified calcium phosphate powder;
step three, preparing a 3D printing material: uniformly mixing organic hectorite modified calcium phosphate powder, glycolide, lactide and stannous isooctanoate in an organic solvent, introducing into a high-temperature reaction kettle, heating to a certain temperature, reacting for a certain time under the condition of heat preservation, stopping reaction, cooling and discharging; and then filtering, adding the obtained filter cake into absolute ethyl alcohol, stirring for a certain time, washing, filtering, drying at a certain temperature to constant weight, and grinding to a certain particle size to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material.
In the above technical scheme, in the first step, the quaternary ammonium salt is one or a combination of two of octadecyl trimethyl ammonium bromide, octadecyl trimethyl ammonium chloride, hexadecyl trimethyl ammonium bromide and hexadecyl trimethyl ammonium chloride in any proportion.
In the above technical scheme, in the second step, the calcium phosphate powder is one or a composition of any two or more of amorphous calcium phosphate, tricalcium phosphate and tetracalcium phosphate in any proportion.
In the above technical scheme, in the third step, the organic solvent is one or a combination of two or more of chloroform, tetrahydrofuran and pyridine in any proportion.
In the above technical scheme, in the first step, organohectorite is prepared: firstly, dispersing 100 parts of hectorite in 300-500 parts of water at the temperature of 60-85 ℃, and simultaneously dispersing 10-30 parts of quaternary ammonium salt in 300-500 parts of water at the temperature of 60-85 ℃ to respectively obtain hot solutions; then mixing the two hot solutions, heating to 90-95 ℃, and stirring for reaction for 1-2 hours; and then washing, filtering and drying at 60-105 ℃ to constant weight to obtain the organohectorite.
In the above technical scheme, in the second step, the organolithium saponite modified calcium phosphate powder is prepared: and (3) adding 5-15 parts of organohectorite prepared in the step one and 40-100 parts of calcium phosphate powder into 300-500 parts of absolute ethyl alcohol, heating to 50-80 ℃, keeping the temperature for 5-8 hours, then washing, filtering, and drying at 100-130 ℃ to constant weight to obtain organohectorite modified calcium phosphate powder.
In the above technical scheme, in the third step, the 3D printing material is prepared: uniformly mixing 100-200 parts of organolithionite modified calcium phosphate powder, 20-50 parts of glycolide, 20-50 parts of lactide and 1-5 parts of stannous isooctanoate in 500-1000 parts of organic solvent, then introducing the mixture into a high-temperature reaction kettle, raising the temperature to 150-180 ℃, carrying out heat preservation reaction for 10-20 hours, stopping the reaction, reducing the temperature and discharging; and then filtering, adding the obtained filter cake into 300-500 parts of absolute ethyl alcohol, stirring for 1-3 hours, washing, filtering, drying at 50-80 ℃ to constant weight, and grinding to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material with the granularity of 2000-10000 meshes.
In the above technical scheme, the water in the first step is pure water.
Compared with the prior art, the invention has the beneficial effects that:
(1) the invention provides a preparation method of a medical polylactic acid in-situ modified calcium phosphate bone cement 3D printing material. The organic modification is performed to improve the compatibility of the calcium phosphate material with the polylactic acid. The organic hectorite and the calcium phosphate are subjected to reflux reaction in absolute ethyl alcohol, and the main purpose is to fully coat the surfaces of calcium phosphate powder particles with organic hectorite platelets. In absolute ethyl alcohol, the organolithium saponite lamellar structure expands, disintegrates and strips, thus generating countless nano lamellar platelets. The filtered absolute ethyl alcohol can be recycled by rectification and other modes. Through the characterization means such as infrared, XRD, SEM and the like, the organohectorite nano-layered platelets are found that a small part of the organohectorite nano-layered platelets is firstly adsorbed in the pore structure on the surface of the calcium phosphate particles, and the rest of the organohectorite nano-layered platelets are superposed and stacked on the surface of the calcium phosphate particles in the modes such as molecular adsorption force, so that an organic layer with certain hydrophobic property is formed. Pure unmodified hectorite can also adsorb and wrap the surface of calcium phosphate powder particles in absolute ethyl alcohol, but the calcium phosphate particles have poor compatibility with polylactic acid and cannot uniformly participate in polylactic acid polymerization reaction at a molecular level. And then uniformly mixing the organohectorite modified calcium phosphate powder, glycolide, lactide and catalyst stannous isooctanoate in organic solvents such as chloroform and the like, then introducing the mixture into a high-temperature reaction kettle, heating to a certain temperature, and carrying out heat preservation reaction for a certain time to generate polylactic acid uniformly mixed with the calcium phosphate molecules. However, at this time, some unreacted monomers and catalyst remained, so that a sufficient amount of absolute ethanol was added to completely remove these impurities. Obviously, the organic solvent and the absolute ethyl alcohol can also be recycled by rectification and the like. The main component of the obtained material is CPC with calcium phosphate as the main active component, and the polylactic acid network penetrates through CPC particles, so that the polylactic acid and CPC are hybridized at the molecular level. Grinding the mixture to a certain granularity to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material.
(2) According to the preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material provided by the invention, the prepared medical polylactic acid in-situ modified calcium phosphate cement 3D printing material retains the original excellent mechanical strength and mechanical property of CPC, and has excellent flexibility by introducing polylactic acid, so that the fundamental defect of high brittleness of a pure CPC material is greatly improved.
(3) According to the preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material, the polylactic acid and the CPC are uniformly mixed on a molecular level scale by virtue of the wrapping of the organolithionite, and the effect of the preparation method is far better than that of physical and mechanical mixing of the polylactic acid and the CPC and the like.
(4) According to the preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material, the polylactic acid component is introduced, so that the advantages of biocompatibility, biodegradability and the like of the modified CPC are more prominent. Therefore, the preparation method has strong practicability and extremely bright industrial prospect.
(5) The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material provided by the invention utilizes an in-situ modification process, and CPC participates in a polylactic acid (PLA) polymerization preparation reaction process, so that PLA modified calcium phosphate bone hybridized and compounded on a molecular level scale is prepared and is used as the medical 3D printing material.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects solved by the present invention more apparent, the present invention is further described in detail below with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1.
A preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material comprises the following steps:
step one, preparing organolithium saponite: firstly, dispersing 100 parts of hectorite in 400 parts of water at 70 ℃, and simultaneously dispersing 20 parts of quaternary ammonium salt in 400 parts of water at 70 ℃ to respectively obtain hot solutions; then mixing the two hot solutions, heating to 93 ℃, and stirring for reaction for 1.5 hours; then washing, filtering and drying at 80 ℃ to constant weight to obtain the organohectorite;
in this example, the quaternary ammonium salt is octadecyl trimethyl ammonium bromide;
wherein the water in the first step is pure water;
step two, preparing the organohectorite modified calcium phosphate powder: adding 10 parts of organohectorite prepared in the step one and 80 parts of calcium phosphate powder into 400 parts of absolute ethyl alcohol, heating to 65 ℃, preserving heat for 7 hours, then washing, filtering, and drying at 125 ℃ to constant weight to obtain organohectorite modified calcium phosphate powder;
in this example, the calcium phosphate powder is amorphous calcium phosphate;
step three, preparing a 3D printing material: uniformly mixing 150 parts of organohectorite modified calcium phosphate powder, 35 parts of glycolide, 35 parts of lactide and 3 parts of stannous isooctanoate in 800 parts of organic solvent, introducing into a high-temperature reaction kettle, heating to 160 ℃, keeping the temperature for reaction for 15 hours, stopping the reaction, cooling and discharging; and then filtering, adding the obtained filter cake into 400 parts of absolute ethyl alcohol, stirring for 2 hours, washing, filtering, drying at 75 ℃ to constant weight, and grinding to 5000 meshes to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material.
In this example, the organic solvent was chloroform.
Example 2.
A preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material comprises the following steps:
step one, preparing organolithium saponite: firstly, dispersing 100 parts of hectorite in 300 parts of water at 60 ℃, and simultaneously dispersing 10 parts of quaternary ammonium salt in 300 parts of water at 60 ℃ to respectively obtain hot solutions; then mixing the two hot solutions, heating to 90 ℃, and stirring for reaction for 1 h; then washing, filtering and drying at 60 ℃ to constant weight to obtain the organohectorite;
in this example, the quaternary ammonium salt is octadecyl trimethyl ammonium chloride;
wherein the water in the first step is pure water;
step two, preparing the organohectorite modified calcium phosphate powder: adding 5 parts of organohectorite prepared in the step one and 40 parts of calcium phosphate powder into 300 parts of absolute ethyl alcohol, heating to 50 ℃, preserving heat for 5 hours, then washing, filtering, and drying at 100 ℃ to constant weight to obtain organohectorite modified calcium phosphate powder;
in this example, the calcium phosphate powder is tricalcium phosphate;
step three, preparing a 3D printing material: uniformly mixing 100 parts of organohectorite modified calcium phosphate powder, 20 parts of glycolide, 20 parts of lactide and 1 part of stannous isooctanoate in 500 parts of organic solvent, introducing into a high-temperature reaction kettle, heating to 150 ℃, keeping the temperature for reaction for 10 hours, stopping the reaction, cooling and discharging; and then filtering, adding the obtained filter cake into 300 parts of absolute ethyl alcohol, stirring for 1h, washing, filtering, drying at 50 ℃ to constant weight, and grinding to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material with the granularity of 2000 meshes.
In this example, the organic solvent is tetrahydrofuran.
Example 3.
A preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material comprises the following steps:
step one, preparing organolithium saponite: firstly, dispersing 100 parts of hectorite in 500 parts of water at 85 ℃, and simultaneously dispersing 30 parts of quaternary ammonium salt in 500 parts of water at 85 ℃ to respectively obtain hot solutions; then mixing the two hot solutions, heating to 95 ℃, and stirring for reaction for 2 hours; then washing, filtering and drying at 105 ℃ to constant weight to obtain the organic hectorite;
in this example, the quaternary ammonium salt is octadecyl trimethyl ammonium chloride;
wherein the water in the first step is pure water;
step two, preparing the organohectorite modified calcium phosphate powder: adding 15 parts of organohectorite prepared in the step one and 100 parts of calcium phosphate powder into 500 parts of absolute ethyl alcohol, heating to 80 ℃, preserving heat for 8 hours, then washing, filtering, and drying at 130 ℃ to constant weight to obtain organohectorite modified calcium phosphate powder;
in this example, the calcium phosphate powder is tetracalcium phosphate;
step three, preparing a 3D printing material: uniformly mixing 200 parts of organohectorite modified calcium phosphate powder, 50 parts of glycolide, 50 parts of lactide and 5 parts of stannous isooctanoate in 1000 parts of organic solvent, introducing into a high-temperature reaction kettle, heating to 180 ℃, keeping the temperature for reaction for 20 hours, stopping the reaction, cooling and discharging; and then filtering, adding the obtained filter cake into 500 parts of absolute ethyl alcohol, stirring for 3 hours, washing, filtering, drying at 80 ℃ to constant weight, and grinding to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material with the granularity of 10000 meshes.
In this example, the organic solvent is pyridine.
Example 4.
A preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material comprises the following steps:
step one, preparing organolithium saponite: firstly, dispersing 100 parts of hectorite in 350 parts of water at 65 ℃, and simultaneously dispersing 15 parts of quaternary ammonium salt in 350 parts of water at 65 ℃ to respectively obtain hot solutions; then mixing the two hot solutions, heating to 91 ℃, and stirring for reaction for 1.8 h; then washing, filtering and drying at 70 ℃ to constant weight to obtain the organic hectorite;
in the embodiment, the quaternary ammonium salt is a composition of cetyl trimethyl ammonium bromide and cetyl trimethyl ammonium chloride according to any proportion;
wherein the water in the first step is pure water;
step two, preparing the organohectorite modified calcium phosphate powder: adding 7 parts of organohectorite prepared in the step one and 50 parts of calcium phosphate powder into 350 parts of absolute ethyl alcohol, heating to 60 ℃, preserving heat for 7 hours, then washing, filtering, and drying at 110 ℃ to constant weight to obtain organohectorite modified calcium phosphate powder;
in this embodiment, the calcium phosphate powder is a composition of amorphous calcium phosphate and tricalcium phosphate in any proportion;
step three, preparing a 3D printing material: uniformly mixing 180 parts of organohectorite modified calcium phosphate powder, 40 parts of glycolide, 40 parts of lactide and 4 parts of stannous isooctanoate in 600 parts of organic solvent, introducing into a high-temperature reaction kettle, heating to 160 ℃, keeping the temperature for reaction for 12 hours, stopping the reaction, cooling and discharging; and then filtering, adding the obtained filter cake into 350 parts of absolute ethyl alcohol, stirring for 1.5 hours, washing, filtering, drying at 60 ℃ to constant weight, and grinding to reach a particle size of 3000 meshes to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material.
In this embodiment, the organic solvent is a combination of chloroform and tetrahydrofuran at any ratio.
Example 5.
A preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material comprises the following steps:
step one, preparing organolithium saponite: firstly, dispersing 100 parts of hectorite in 450 parts of water at the temperature of 80 ℃, and simultaneously dispersing 25 parts of quaternary ammonium salt in 450 parts of water at the temperature of 80 ℃ to respectively obtain hot solutions; then mixing the two hot solutions, heating to 94 ℃, and stirring for reaction for 1.8 h; then washing, filtering and drying at 90 ℃ to constant weight to obtain the organohectorite;
in the embodiment, the quaternary ammonium salt is a composition of octadecyl trimethyl ammonium chloride, hexadecyl trimethyl ammonium bromide and hexadecyl trimethyl ammonium chloride according to any proportion;
wherein the water in the first step is pure water;
step two, preparing the organohectorite modified calcium phosphate powder: adding 12 parts of organohectorite prepared in the step one and 90 parts of calcium phosphate powder into 450 parts of absolute ethyl alcohol, heating to 70 ℃, preserving heat for 7 hours, then washing, filtering, and drying at 120 ℃ to constant weight to obtain organohectorite modified calcium phosphate powder;
in this embodiment, the calcium phosphate powder is a composition of amorphous calcium phosphate, tricalcium phosphate and tetracalcium phosphate in any proportion;
step three, preparing a 3D printing material: uniformly mixing 180 parts of organohectorite modified calcium phosphate powder, 40 parts of glycolide, 45 parts of lactide and 2 parts of stannous isooctanoate in 900 parts of organic solvent, introducing into a high-temperature reaction kettle, heating to 170 ℃, keeping the temperature for reacting for 18 hours, stopping the reaction, cooling and discharging; and then filtering, adding the obtained filter cake into 450 parts of absolute ethyl alcohol, stirring for 2.5 hours, washing, filtering, drying at 70 ℃ to constant weight, and grinding to 9000 meshes to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material.
In this embodiment, the organic solvent is a combination of chloroform, tetrahydrofuran and pyridine at any ratio.
Experiment:
various comparative tests were carried out on the medical polylactic acid in-situ modified calcium phosphate cement 3D printing materials A to D prepared in examples 1 to 4 and the similar products imported from abroad (model: Jet-2A, manufactured by Collplant biology 3D printing company, Israel) and the results are shown in the following Table 1.
TABLE 13D printed Material Performance comparison test results
| Test index | A | B | C | D | Jet-2A |
| Flexural Strength (MPa) | 1.2 | 1.5 | 1.5 | 1.6 | 0.9 |
| Compressive strength (MPa) | 8.3 | 8.5 | 8.1 | 8.0 | 7.7 |
| Flexibility (mm) | 0.5 | 0.5 | 0.5 | 0.5 | 2 |
| Printing precision (mm) | 0.2 | 0.1 | 0.2 | 0.2 | 0.4 |
As can be seen from Table 1, the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material prepared by the method has the advantages of excellent performance indexes such as mechanical strength, mechanical property and flexibility, and is obviously better than the performance of similar products imported abroad at present. Therefore, the preparation process has bright industrial prospect and can create huge economic benefit.
Although the present invention has been described in detail with reference to the preferred embodiments, it will be understood by those skilled in the art that various changes, modifications and equivalents may be made therein without departing from the spirit and scope of the invention.
Claims (8)
1. A preparation method of a medical polylactic acid in-situ modified calcium phosphate cement 3D printing material is characterized by comprising the following steps: it comprises the following steps:
step one, preparing organolithium saponite: firstly, dispersing hectorite in water at a certain temperature, and simultaneously dispersing quaternary ammonium salt in the water at the certain temperature to respectively obtain hot solutions; then mixing the two hot solutions, heating to a certain temperature, stirring and reacting for a certain time; then washing, filtering and drying at a certain temperature to constant weight to obtain the organohectorite;
step two, preparing the organohectorite modified calcium phosphate powder: adding the organohectorite and calcium phosphate powder prepared in the step one into absolute ethyl alcohol, heating to a certain temperature, keeping the temperature for a certain time, then washing, filtering, and drying at a certain temperature to constant weight to obtain organohectorite modified calcium phosphate powder;
step three, preparing a 3D printing material: uniformly mixing organic hectorite modified calcium phosphate powder, glycolide, lactide and stannous isooctanoate in an organic solvent, introducing into a high-temperature reaction kettle, heating to a certain temperature, reacting for a certain time under the condition of heat preservation, stopping reaction, cooling and discharging; and then filtering, adding the obtained filter cake into absolute ethyl alcohol, stirring for a certain time, washing, filtering, drying at a certain temperature to constant weight, and grinding to a certain particle size to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material.
2. The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material according to claim 1, which is characterized by comprising the following steps: in the first step, the quaternary ammonium salt is one or a composition of two of octadecyl trimethyl ammonium bromide, octadecyl trimethyl ammonium chloride, hexadecyl trimethyl ammonium bromide or hexadecyl trimethyl ammonium chloride according to any proportion.
3. The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material according to claim 1, which is characterized by comprising the following steps: in the second step, the calcium phosphate powder is one or a composition of more than two of amorphous calcium phosphate, tricalcium phosphate or tetracalcium phosphate according to any proportion.
4. The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material according to claim 1, which is characterized by comprising the following steps: in the third step, the organic solvent is one or a combination of more than two of chloroform, tetrahydrofuran or pyridine according to any proportion.
5. The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material according to claim 1, which is characterized by comprising the following steps: in the first step, preparing organohectorite: firstly, dispersing 100 parts of hectorite in 300-500 parts of water at the temperature of 60-85 ℃, and simultaneously dispersing 10-30 parts of quaternary ammonium salt in 300-500 parts of water at the temperature of 60-85 ℃ to respectively obtain hot solutions; then mixing the two hot solutions, heating to 90-95 ℃, and stirring for reaction for 1-2 hours; and then washing, filtering and drying at 60-105 ℃ to constant weight to obtain the organohectorite.
6. The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material according to claim 1, which is characterized by comprising the following steps: in the second step, preparing organolithium saponite modified calcium phosphate powder: and (3) adding 5-15 parts of organohectorite prepared in the step one and 40-100 parts of calcium phosphate powder into 300-500 parts of absolute ethyl alcohol, heating to 50-80 ℃, keeping the temperature for 5-8 hours, then washing, filtering, and drying at 100-130 ℃ to constant weight to obtain organohectorite modified calcium phosphate powder.
7. The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material according to claim 1, which is characterized by comprising the following steps: in the third step, preparing a 3D printing material: uniformly mixing 100-200 parts of organolithionite modified calcium phosphate powder, 20-50 parts of glycolide, 20-50 parts of lactide and 1-5 parts of stannous isooctanoate in 500-1000 parts of organic solvent, then introducing the mixture into a high-temperature reaction kettle, raising the temperature to 150-180 ℃, carrying out heat preservation reaction for 10-20 hours, stopping the reaction, reducing the temperature and discharging; and then filtering, adding the obtained filter cake into 300-500 parts of absolute ethyl alcohol, stirring for 1-3 hours, washing, filtering, drying at 50-80 ℃ to constant weight, and grinding to obtain the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material with the granularity of 2000-10000 meshes.
8. The preparation method of the medical polylactic acid in-situ modified calcium phosphate cement 3D printing material according to claim 1, which is characterized by comprising the following steps: the water in the step one is pure water.
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| CN101302282A (en) * | 2008-06-30 | 2008-11-12 | 新疆大学 | Intercalation polymerization polylactic acid-organophilicsoapstone composite material and preparation thereof |
| CN101773690A (en) * | 2010-03-11 | 2010-07-14 | 浙江大学 | Polylactic acid based/20nm calcium phosphate composite stent material and preparation method thereof |
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